Benzocaine is the ethylester of p-aminobenzoic acid (PABA). It can be prepared from PABA and ethanol by Fischer esterification or via the reduction of ethyl p-nitrobenzoate. Benzocaine is sparingly soluble in water; it is more soluble in dilute acids and very soluble in ethanol, chloroform and ethyl ether. The melting point of benzocaine is 88–90 °C, and the boiling point is about 310 °C. The density of benzocaine is 1.17 g/cm3.
Benzocaine was first synthesized in 1890 by the German chemist Eduard Ritsert (1859–1946), in the town of Eberbach and introduced to the market in 1902 under the name "Anästhesin".
Mechanism of action
Pain is caused by the stimulation of free nerve endings. When the nerve endings are stimulated, sodium enters the neuron, causing depolarization of the nerve and subsequent initiation of an action potential. The action potential is propagated down the nerve toward the central nervous system, which interprets this as pain. Benzocaine acts to inhibit the voltage-dependent sodium channels (VDSCs) on the nerve membrane, stopping the propagation of the action potential.
Over-application of oral anesthetics such as benzocaine can increase the risk of pulmonary aspiration by relaxing the gag-reflex and allowing regurgitated stomach contents or oral secretions to enter the airway. Applying an oral anesthetic and consuming beverages before going to bed can be particularly hazardous. The oral use of benzocaine products has been found to be a cause of methemoglobinemia, a disorder in which the amount of oxygen carried by the blood is greatly reduced. This side effect is most common in children under 2 years of age.
Benzocaine may cause allergic reactions. It is a chief allergen of Balsam of Peru, which a number of surveys have identified as being in the "top five" allergens most commonly causing patch test reactions in people referred to dermatology clinics.
Benzocaine is used as a key ingredient in numerous pharmaceuticals:
Over the counter throat lozenges such as Anbesol and Cepacol.
Some glycerol-based ear medications for use in removing excess wax as well as relieving ear conditions such as otitis media and swimmers ear.
Some condoms designed to prevent premature ejaculation. Benzocaine largely inhibits sensitivity on the penis, and can allow for an erection to be maintained longer (in a continuous act) by delaying ejaculation. Conversely, an erection will also fade faster if stimulus is interrupted.
Benzocaine mucoadhesive patches have been used in reducing orthodontic pain.
Benzocaine is commonly found, particularly in Britain, as an impurity in street cocaine. Whilst giving a numbing effect similar to cocaine on users' gums it does not actually produce the effects of cocaine. But in terms of an orally based saliva drug test benzocaine can and has been mistaken for a false positive for cocaine.
^Demare, Patricia; Regla, Ignacio (2012). "Synthesis of Two Local Anesthetics from Toluene: An Organic Multistep Synthesis in a Project-Oriented Laboratory Course". Journal of Chemical Education89: 147. doi:10.1021/ed100838a.
^Ritsert, E. (1925) "Über den Werdegang des Anästhesins" (On the development of Anästhesin), Pharmazeutische Zeitung, vol. 60, pages 1006–1008. See also: Christoph Friedrich and Magdalena Klimonow, "150. Geburtstag: Eduard Ritsert und das Anaesthesin" (150th birthday: Eduard Ritsert and Anästhetsin [Benzocaine]"), Pharmazeutische Zeitung online. First published clinical study demonstrating the efficacy of benzocaine: Noorden, C. v. (1902) "Ueber para-Aminobenzoesäure-Ester als locales Anästhetikum" (On [an] ester of para-aminobenzoic acid as a local anaesthetic), Klinische Wochenschrift, vol. 39, pages 373–375.
^Eslamian L, Borzabadi-Farahani A, Edini HZ, Badiee MR, Lynch E, Mortazavi A. (2013). "The analgesic effect of benzocaine mucoadhesive patches on orthodontic pain caused by elastomeric separators, a preliminary study.". Acta Odontol Scand.71 (5): 1168–73. doi:10.3109/00016357.2012.757358. PMID23301559.